Interactions between sleep and learning in Drosophila melanogaster: what is the role of PDF target neurons? Understanding the nature and purpose of sleep is currently one of the major goals in neuroscience research. It is clear that sleep is regulated by a combination of circadian and homeostatic systems, and that sleep and memory formation are tightly linked. However, it remains unclear what mechanisms at the circuit and molecular levels mediate these interactions. In the studies proposed here, the powerful Drosophila model system will be used to tackle these issues. It has recently been shown that a cluster of cells once thought to be purely part of the circadian system also play a role in homeostatic sleep regulation. These are the ventral lateral neurons (LNvs), which produce the peptide neurotransmitter PDF. However, it is unknown what the crucial targets of these cells are, or if they are involved in signaling that an organism needs additional sleep following sleep deprivation or learning. By combining genetic manipulations to both increase and decrease the excitability of LNv target cells with cutting edge electrophysiological recordings, this research will expand our understanding of the circuit- and molecular-level strategies that animals use to modulate sleep and memory formation. PUBLIC HEALTH RELEVANCE: Sleep disturbances are highly prevalent in today's society, resulting from shift work, sleep disorders, aging, psychiatric disorders, or simply from an extremely busy lifestyle. Understanding what strategies the brain uses to regulate the amount and quality of sleep that an animal obtains is therefore of urgent importance from a public health standpoint. The proposed research will address this issue by examining the mechanisms used to regulate sleep in response to sleep deprivation and learning experiences.